Compositions comprising anti-cd38 antibodies and carfilzomib

Abstract

Disclosed herein are compositions and kits which comprise anti-CD38 antibodies and carfilzomib compounds. Also disclosed are methods for treating cancers, such as multiple myeloma, in subjects with the compositions and kits.

What is claimed is: 
     
         1 . A method of treating a cancer in a subject which comprises
 administering one or more anti-CD38 antibodies and one or more carfilzomib compounds to the subject.   
     
     
         2 . The method of  claim 1 , wherein the cancer is a hematological malignancy. 
     
     
         3 . The method of  claim 1 , wherein the cancer is multiple myeloma. 
     
     
         4 . The method of  claim 1 , wherein the cancer is a relapsed multiple myeloma or a refractory multiple myeloma. 
     
     
         5 . The method of  claim 1 , wherein the one or more carfilzomib compounds is carfilzomib. 
     
     
         6 . The method of  claim 1 , wherein the one or more anti-CD38 antibodies are administered in an effective amount, preferably a synergistic amount. 
     
     
         7 . The method of  claim 1 , wherein the one or more anti-CD38 antibodies and/or the one or more carfilzomib compounds are administered in a therapeutically effective amount. 
     
     
         8 . The method of any one of  claims 1  to  7 , wherein at least one of the one or more anti-CD38 antibodies is capable of killing a CD38 +  cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC). 
     
     
         9 . The method of any one of  claims 1  to  7 , wherein at least one of the one or more anti-CD38 antibodies comprises one or more complementarity-determining region having an amino acid sequence selected from the group consisting of SEQ ID NOs: 13, 14, 81, 15, 16, 17, 18, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 and 36. 
     
     
         10 . The method of any one of  claims 1  to  7 , wherein at least one of the one or more anti-CD38 antibodies is selected from the group consisting of:
 a) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 13, 15 and either SEQ ID NO: 14 or SEQ ID NO: 81, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 16, 17 and 18; 
 b) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 25, 26 and 27, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 28, 29 and 30; 
 c) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 1, 2 and 3, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 4, 5 and 6; 
 d) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 7, 8 and 9, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 10, 11 and 12; 
 e) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 19, 20 and 21, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 22, 23 and 24; and 
 f) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 31, 32 and 33, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 34, 35 and 36. 
 
     
     
         11 . The method of  claim 10 , wherein said antibody comprises a heavy chain having a V H  variable region represented by SEQ ID NO: 66, and a light chain having a V L  variable region represented by either SEQ ID NO: 62 or SEQ ID NO: 64. 
     
     
         12 . The method of  claim 10 , wherein said antibody comprises a heavy chain having a V H  variable region represented by SEQ ID NO: 72, and a light chain having a V L  variable region represented by either SEQ ID NO: 68 or SEQ ID NO: 70. 
     
     
         13 . The method of any one of  claims 1  to  12 , wherein the one or more anti-CD38 antibodies is administered intravenously. 
     
     
         14 . The method of any one of  claims 1  to  12 , wherein the one or more carfilzomib compounds is administered intravenously. 
     
     
         15 . The method of any one of  claims 1  to  14 , wherein the one or more anti-CD38 antibodies and the one or more carfilzomib compounds are administered sequentially. 
     
     
         16 . The method of any one of  claims 1  to  15 , and further comprising administering a dexamethasone compound, preferably dexamethasone, to the subject. 
     
     
         17 . The method of  claim 16 , wherein the dexamethasone compound is administered orally. 
     
     
         18 . The method of any one of  claims 16  to  17 , wherein the one or more anti-CD38 antibodies, the one or more carfilzomib compounds, and the dexamethasone compound are administered sequentially. 
     
     
         19 . A composition comprising
 a) at least one anti-CD38 antibody, preferably the antibody is capable of killing a CD38 +  cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC); and   b) at least one carfilzomib compound, preferably carfilzomib; and, optionally   c) a dexamethasone compound, preferably dexamethasone.   
     
     
         20 . A kit comprising
 a) a first composition comprising at least one anti-CD38 antibody, preferably the antibody is capable of killing a CD38 +  cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC); and   b) a second composition comprising at least one carfilzomib compound, preferably carfilzomib.   
     
     
         21 . The kit of  claim 20 , wherein the compositions are packaged for sequential administration to a subject. 
     
     
         22 . The kit of  claim 20  or  claim 21 , and further including a dexamethasone compound, preferably dexamethasone. 
     
     
         23 . The kit of  claim 22 , wherein the dexamethasone compound is packaged for sequential administration to a subject. 
     
     
         24 . A kit comprising
 at least one anti-CD38 antibody capable of killing a CD38 +  cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC), packaged together with   a label having one or more messages that the at least one anti-CD38 antibody shall be administered in combination with carfilzomib, and optionally with dexamethasone.   
     
     
         25 . A combination of:
 (i) at least one anti-CD38 antibody, preferably the antibody is capable of killing a CD38+ cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC); and   (ii) at least one carfilzomib compound, preferably carfilzomib; and, optionally   (iii) a dexamethasone compound, preferably dexamethasone.   
     
     
         26 . The combination of  claim 25 , wherein the combination is for sequential use in the treatment of a hematological malignancy, preferably multiple myeloma.